Introduction to Diabetes and Metabolism Markers.

Georgina Grimsey

Nov 22, 2019

Metabolism is the set of life-sustaining chemical
transformations within the cells. The three main purposes of metabolism are:
the conversion of food to energy to run cellular processes, the conversion of
food to building blocks for proteins, lipids, nucleic acids, and some
carbohydrates, and the elimination of wastes. These enzyme-catalysed reactions
allow organisms to grow and reproduce, maintain their structures, and respond
to their environments. The word metabolism can also refer to the sum of all
chemical reactions that occur in living organisms, including digestion and the
transport of substances into and between different cells.

When there is an anomaly in one of these metabolic
processes, disease may occur. Diabetes is one of the most prominent examples of
a metabolic disease, characterized by either the failure of pancreatic beta
cells to produce insulin adequately (type I), or the failure to respond to
insulin adequately (type II). Either way, the consequence is prolonged high
blood sugar levels with serious long-term complications including
cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage
to the eyes.

Elevated levels of high molecular weight Adiponectin forms
are associated with lower risk of diabetes, while elevated levels of HbA1c
indicate elevated blood sugar as in diabetes. C-peptide levels would be a
measure of insulin production.  Aberrant
levels of Albumin indicate generic health issues, and of Ferritin and
Transferrin indicate anaemia, changed levels of ApoA1 and ApoB are more
indicative of cardiovascular disease.

Adiponectin

Adiponectin is expressed and secreted by adipose tissue and
placenta. Its plasma levels are relatively high compared to other hormones.
Levels are inversely correlated to percentage of body fat in adults. It is
involved in regulating glucose levels as well as fatty acid breakdown. Adiponectin automatically self-associates
into larger homomeric structures. The levels of such high molecular weight
forms are associated with a lower risk of diabetes, but with a higher risk of
coronary artery disease.

Serum Albumin

Serum albumin, the main protein of plasma, has a good
binding capacity for water, cations, but also functions as a carrier of
hydrophobic molecules like fatty acids, lipid-soluble hormones, bilirubin, and
drugs. Its main function is the regulation of the colloidal osmotic pressure of
blood and blood volume. Low albumin levels may be caused by liver disease,
nephrotic syndrome, burns, protein-losing enteropathy, malabsorption,
malnutrition, late pregnancy, or genetic malignancies. High albumin levels
indicate dehydration.

Apolipoprotein A1 (ApoA1)

ApoA1 is the major component of High-Density Lipoproteins
(HDL) particles in plasma. ApoA1 helps to clear cholesterol from arteries: It enables removal of fat molecules from
within cells (including macrophages within the walls of arteries which have
become overloaded with fats from oxidized LDL particles) for transport to
elsewhere, including back to LDL particles or to the liver for excretion. ApoA1
is often used as a biomarker for prediction of cardiovascular diseases. As an
HDL marker, its ratio with ApoB100 (LDL marker) has a very strong correlation
with myocardial infarction events.

Apolipoprotein B (ApoB)

ApoB is the
primary component of Low-Density Lipoproteins (LDL, or “bad cholesterol”),
which is responsible for carrying cholesterol to tissues. Through yet unknown
mechanisms, high levels of ApoB can lead to plague formation in artery walls
causing cardiovascular disease (atherosclerosis). Levels of ApoB is a more
reliable indicator than total cholesterol or LDL, and the liver-specific
isoform ApoB100 is used in combination with ApoA1 to predict myocardial
infarction.

C-peptide

The C-peptide is a product derived from the insulin precursor
during the maturation process in the pancreatic beta cells. Because each
molecule of matured insulin is produced and secreted together with one molecule
of C-peptide, the latter became a marker for insulin production/secretion. However, C-peptide has been found to be a
bioactive peptide itself with effects on microvascular blood flow and tissue
health.

 

Ferritin

Ferritin is a universal intracellular protein, found in most
organisms, that stores iron and releases it in a controlled fashion. In humans,
it acts as a buffer against iron deficiency and iron overload. Ferritin is
found in most tissues as a cytosolic protein, but small amounts are secreted
into the serum where it functions as an iron carrier. Because levels of plasma
ferritin indirectly indicate the total amount of iron stored in the body, serum
ferritin is used as a diagnostic test to measure iron-deficiency as result of anaemia
and chronic disease.

Glycated haemoglobin (HbA1c)

Glycated haemoglobin is formed in a
non-enzymatic process during exposure to plasma glucose. Consequently, normal
levels of glucose produce a normal amount of glycated haemoglobin and when the
levels of plasma glucose increase, the fraction of glycated haemoglobin
increases proportionately. Thus, HbA1c
is measured primarily to identify
the average plasma glucose concentration over prolonged periods of time. Higher
levels are found in people with persistently elevated blood sugar levels, like
with diabetes.

Transferrin

Transferrins are glycoproteins regulating the amount of free
iron in circulation. Each transferrin molecule binds two Fe3+-ions
with high affinity. The Apotransferrin holds no iron. Transferrin levels
elevate with anaemia, pregnancy, and during use of birth control pills. Levels
will drop by chronic infections, malignant growth, alcohol-induced liver damage
and conditions resulting in protein loss.

Inflammation marker

Lactoferrin (LF)

Lactoferrin is one of the transferrin proteins that transfer
iron to the cells and control the level of free iron in the blood and external
secretions. Also known as lactotransferrin (LTF), it is a major component in
milk and in other exocrine secretions of mammals, such as saliva, bile, tears,
and pancreas.  For its antimicrobial
properties, it is part of the innate immune system protecting infants from
infection through breast feeding, colostrum (first milk) having the highest LF
concentration.

LF is also expressed in granulocytes and in small intestine
epithelial cells. Upon bacterial infection, LF is released into the intestinal
lumen. Lactoferrin, often in combination with Calprotectin, is measured in a
faecal test to detect inflammation in the intestine. Lactoferrin levels are
associated with disease severity in Intestinal Bowel Disease (IBD).

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